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We used the lead compound
2023-12-12
We used the lead compound C4 to demonstrate that small molecule ACL inhibitors can recapitulate ACL knockdown (KD) in modulation of cancer stemness. We have shown previously that ACL KD reduced the CSC population in multiple cancer cell lines. The E-snail cells are an established CSC model system. E
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br Telmisartan Telmisartan is one
2023-12-12
Telmisartan Telmisartan is one of the widely used antihypertensive agents, which has demonstrated favorable safety and tolerability profiles, both alone and in combination therapies. It has a number of pharmacological properties that distinguish it from other ARBs—the longest plasma half-life, hi
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Helioxanthin derivative 5-4-2 Hyperactivity of the hypothala
2023-12-12
Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is well described in MDD (Pariante and Lightman, 2008, Marques et al., 2009), is also observed in AD and results in increased glucocorticoid (GC, cortisol in primates) levels in blood and CSF (Davis et al., 1986, Martignoni et al.
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Recent studies suggest that A caused synapse damage as a
2023-12-12
Recent studies suggest that Aβ caused synapse damage as a consequence of aberrant cell signalling. As synthetic Aβ42 monomers activate the phosphatidylinositol-3-kinase pathway (Giuffrida et al., 2009) and insulin signalling (Giuffrida et al., 2012) it is possible that Aβ monomers and Aβ oligomers a
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Here we found that AMPK directly phosphorylates
2023-12-12
Here we found that AMPK directly phosphorylates EZH2 at Thr311 to disrupt its interaction with SUZ12 and to inhibit PRC2 enzymatic activity, which is supported by the increased expression of PRC2-repressed genes. Furthermore, the T311E-EZH2 mutant that mimics AMPK-mediated phosphorylation status sup
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This study demonstrates numerical alterations
2023-12-12
This study demonstrates numerical alterations of creatinine levels potentially reflecting ongoing or even higher myocardial contraction of the LAA after successful LAAC. Creatinine is the direct breakdown product of creatine in muscle, the key metabolite for energy supply during muscular and myocard
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In this study we designed
2023-12-12
In this study, we designed and synthesized two ALK PROTACs (degraders), 5 (MS4077) and 6 (MS4078), by linking ceritinib and pomalidomide [45] through two different linkers. Using human ALCL and NSCLC cells, we characterized both compounds in a battery of assays to demonstrate their effects on reduci
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Another open question is whether GABA and
2023-12-11
Another open question is whether GABA and ACh are released from the same synaptic vesicles, or even the same presynaptic terminals. Multi-transmitter neurons may either function through co-release, in which multiple neurotransmitters are packaged into the same presynaptic terminal and are therefore
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Molecular docking is widely used to predict the interaction
2023-12-11
Molecular docking is widely used to predict the interaction between an enzyme and its inhibitors. This is a computational simulation approach that can be used as a tool to investigate the structure-activity relationship of ACE inhibitory peptides (Goodsell, 2009). It has been recently shown that ACE
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The relative stereochemistry of both the major and minor dia
2023-12-11
The relative stereochemistry of both the major and minor diastereoisomer of (±)-2-(hydroxymethyl)blebbistatin (±)- (and thus (±)-2-(allyloxymethyl)blebbistatin (±)-) was determined with 1D-NOESY experiments (), as crystallization efforts failed. These experiments revealed an interaction between H an
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keap1-nrf2 pathway Recruitment of the Rad BP
2023-12-11
Recruitment of the Rad9/53BP1 mediator to keap1-nrf2 pathway involves multiple pathways (Fig. 2). In unperturbed conditions, Rad9 is already bound to chromatin via interaction between its Tudor domain and methylated histone H3 at lysine 79 [82], [83], [84], [85]. This constitutive Rad9 recruitment
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phenylephrine hydrochloride br Experimental section br Ackno
2023-12-11
Experimental section Acknowledgements Introduction DJ-1 is a highly conserved, homodimeric protein that was originally cloned as an oncogene capable of transforming phenylephrine hydrochloride in cooperation with activated ras[1]. DJ-1 is over-expressed in multiple tumor types and is posit
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Furthermore we also found that the basic level of
2023-12-11
Furthermore, we also found that the basic level of ROS was markedly lower in mtDNA-reduced SW480 tamoxifen citrate than that in the parent cells. Endogenous ROS is most notably produced at the sites of complex I and complex III [5], it might be plausible that the decreased quantity of ROS observed
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Despite the absence of disulfide bonds in
2023-12-11
Despite the absence of disulfide bonds in its linear structure, KT43C displays antifungal and antibacterial activity. Disulfide bonds are determinants of defensins' integrity and have been reported to increase the antimicrobial activity (Jenssen et al., 2006). However, some linear derivatives of AM
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INT-777 australia Introduction The burden of cardiovascular
2023-12-11
Introduction The burden of cardiovascular disease (CVD) is undisputed, accounting for approximately a third of global deaths (17.5 million people in 2012) (WHO, 2012). Atherosclerosis leads to the development of coronary heart disease (CHD) which accounts for more than 40% of these deaths (WHO, 201
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